By E. Frithjof. Wittenberg University.
And all somatic cells in adult worms are postmitotic tadalis sx 20mg, so that studying the aging biology of actively replicat- ing cells is not possible with worms tadalis sx 20 mg. Although not as genetically tractable and short-lived as worms 20mg tadalis sx, they are considerably more tractable and shorter-lived than any vertebrate 20 mg tadalis sx. Moreover , they are behaviorally much more complex than worms , facilitating assessment of cognitive as well as physical aging  . Flies also have real organ systems like eyes , heart , and Malpighian tubules that have analogs if not homologs in vertebrates . Their dietary requirements are much clearer and have been extensively investigated [20, 21]. Monitoring and controlling food intake in ies is not routinely done, but tech- niques are available to do so  and if employed would add considerably to the utility of the model. Adult ies, while being mostly composed of postmitotic cells, also have several pools of stem cells, which allow the study of tissue maintenance by cell replacement. In particular, the Drosophila genetic toolkit can be deployed to understand stem cell dynamics and functional changes with age [23, 24 ]. Numerous similarities have been identied between y and mammalian stem cell behavior . Basic aging research is no The Geroscience Hypothesis: Is It Possible to Change the Rate of Aging? The longevity and disease prole of mouse strains a strain is the product of at least 20 generations of brother-sister inbreeding varies considerably . Some strains should be strenuously avoided for aging research because they are particularly prone to die early of a single spe- cic disease , meaning that studies of those strains are useful for investigating the disease process but not informative with respect to generalized aging processes. The presumed advantage of standardization, facilitating comparison of experimental results among laboratories and between studies, is purchased at the expense of gen- erality. One never knows if a result is an idiosyncrasy of a particular genetic back- ground or is a more general phenomenon. Like many laboratory strains, they exhibit defective melatonin synthesis due to mutations in both necessary biosynthetic enzymes . So over-reliance on any single mouse strain or sub-strain limits our ability to spot cryp- tic aberrancies affecting what is classied as a healthy state. One approach to the problem of cryptic strain idiosyncrasies that combines some generality with some genetic control is the use of genetically heterogeneous mice generated in a repeatable fashion. Originally created for gene mapping studies, this stock is created by interbreeding two F1 hybrids of inbred strains. The resultant F2 mice are each genetically unique full siblings representing a broad swathe of genetic diversity within the laboratory mouse. One reason that inbred mouse strains became so popular was the belief that they would be phenotypically more uniform that outbred populations. Over-reliance on a single genetic background is not a research phenomenon con- ned to mice or to aging research. However both mice and y researchers have discov- ered that genetic background makes a dramatic difference in the impact of longevity interventions. Austad in adult y motorneurons signicantly increased longevity in both males and females, by approximately 30 % and 40 %, respectively, in a particular laboratory strain. However the same mutation introduced into ten inbred, wild-caught strain found that females lived signicantly longer in only 6 of the 10 strains and male lived longer in only 1 of the 10 strains compared to controls [36 ]. Together they rep- resent more than 600 million years of evolutionary divergence from one another. Does this mean that these species are sufcient for investigating both fundamental aging processes and age-related disease pro- cesses relevant to people? I would argue that these species are not enough for either and that we need to expand the traditional bestiary of aging models for the following reasons. First, our workhorse invertebrate models have undergone extensive gene loss since their divergence from our common ancestor. This can be seen by noting that more than 10 % of genes identied in a more distant human relative, the cnidar- ian Acropora millepora, have clear human orthologs that are missing from worm and y genomes . Thus there is a genomic universe of unknown size that may be relevant to aging processes not susceptible to investigation in worms or ies. Additionally, worms have no somatic cell division in adulthood and ies have lim- ited cell division or regenerative capacity. Consequently, a key anti-senescence pro- cess regenerative capacity is difcult to study in these species. Finally with respect to these traditional invertebrate models, both worms and ies employ spe- cialized nonaging life history stages during times of environmental stress (dauer in worms, reproductive diapause in ies) which have no human equivalent. Partial induction of these stages could retard aging via mechanisms not available to humans. In this sense, worm and y ndings could provide false clues to a deeper under- standing of human aging biology. Second, the use of the laboratory mouse as the sole representative of our own mammal clade warrants rethinking. Mice are the main species we rely on to model specic human disease processes and develop interventions to mitigate these pro- cesses. Alzheimer s disease is the most spectacu- lar example of translational failure, with more than 300 drugs showing signicant benet in mouse models, but to date none have replicated that promise in humans . A largely unexplored possibility that warrants attention is that mouse disease The Geroscience Hypothesis: Is It Possible to Change the Rate of Aging? Even the latest onset of these is barely in the comparable range of age as a fraction of lifespan of the most aggressive human familial mutation . It may be that aging is a critical component of the disease etiology, say for instance, requir- ing some vascular injury as an initiating event. Third, all model organisms currently used in aging research are distinguished by their lack of success in resisting fundamental aging processes. That is one of their advantages for the type of aging research that requires lifespan studies. Some species are already well-known for their exception- ally long and healthy lifespans in the natural world and for being able to resist aging processes much better than the longest-lived, most robust model species. So a com- plementary research paradigm is to investigate the cellular mechanisms underlying their resistance [49 51]. Given the phenomenal advances in sequencing power in recent years, insight into the genomes and transcriptomes of some of these excep- tionally senescence-resistance organisms as well as tools for their further investiga- tion could follow rapidly. I stated rather blithely above that the promise of medical interventions that enhance and lengthen healthy life is no longer an empty promise. Lifespan has approximately doubled, for instance, in the 6 million years since humans split from our chimpanzee ancestors. However, this evidence is not completely satisfactory as change over that time period could involve hundreds to thousands of variations in genes or gene expres- sion. By far the most compelling evidence presented below is that we now are able to lengthen life and enhance a number of aspects of health in multiple ways by simple interventions in model organisms in the laboratory. Some of those ways are likely not to be relevant to humans, who are after all, many times more successful at resisting aging than any of our model organisms. The hope is that some of our suc- cesses with model animals will be relevant and translatable to humans and the more targets we identify in animals, the more likely this will be. Generally these studies found increases in both mean and maximum longevity (dened in the rest of this chapter as the longest-lived 10 % of the population) in both sexes and gradually over the next several decades information accumulated that many, although not all, maladies of aging laboratory rodents were also delayed . This thought also illustrates how difcult it is to translate the circumstances of laboratory animals into human terms. Control animals in the study that nds a survival effect weigh roughly 6 11 % more than the national average for captive monkeys of the same species whereas control animals in the study that nds no effect are roughly 8 16 % below the national average. Captive monkeys, in fact captive mammals of virtually all species including mice, are typi- cally obese compared to animals in the wild [57, 58]. So how to think about the results in terms of which animals should be considered obese, which normal, which The Geroscience Hypothesis: Is It Possible to Change the Rate of Aging? Like many a clean and neat hypothesis before it, the reduced metabolism hypothesis crashed on the rocks of experimentation and biological complexity. A number of other simple physiological hypotheses were advanced by logic and slain by experimentation, including the glucocorticoid cascade hypothesis [65, 66 ] and the advanced glycation end-products hypothesis [67, 68]. Several reports that restriction of sulfhydryl-containing amino acids in otherwise isocaloric diets extended mean and maximum longevity in the F344 rats were pub- lished in the 1990s, but in the early 2000s these studies were extended to several rat 14 S. Second, median longevity, though unrelated to total caloric intake, was related to the balance of macronutrients. Specically, mice lived longer when fed diets that were low in protein and high in carbohydrates. Whether the lengthened lifespan associated with reduced protein consumption was due to reduced consumption of specic amino acids as the earlier studies might suggest, was not investigated. It should be noted that this was a single study with a single mouse genotype with modest sample sizes for each of the 25 dietary/survival groups. Nevertheless when combined with the methionine restric- tion studies published earlier, and the invertebrate studies discussed below, it cer- tainly calls into question the traditional wisdom that calories not specic macronutrients are what modulate lifespan. The results were strikingly similar to ndings with respect to variation in replicative lifespan in 166 single gene deletion strains in yeast . The mouse results should be considered preliminary, as the number of individual lifespans per treatment and strain was small (N = 5 in one study, N = 10 12 in the other) and the strain results varied some- what between facilities. In addi- tion, because y and worm lifespans are short and large numbers of animals can be The Geroscience Hypothesis: Is It Possible to Change the Rate of Aging? The data are from 41 recombinant inbred lines derived from an original cross of 8 laboratory strains followed by divergent selection for alcohol sensitivity (Reproduced with permission from Liao et al. Austad laboratory rodents and invertebrates is an assumption that has yet to be validated. Both fruit ies and worms had previously been shown to respond to reduced food availability with longer life [85, 86]. In rodents, it is well-known what their natural diet consists of (seeds plus associated insect larvae) and there had been years of investigation into formu- lating healthy diets, even specialized breeding versus maintenance diets . The normal laboratory diet of fruit ies is an agar-base combination of yeast, sugar or molasses, cornmeal, and other carbohydrates . There is no true standard laboratory diet and the nutrient concentration of the food can vary as much as tenfold among laboratories. Flies typically eat only 1 2 g of food daily, so quantifying food consumption is technically challenging, although possible . Given the different nutrient concentrations of different laboratories standard diets, nutrient consumption of standard-fed ies can vary dramatically among laboratories. However as y nutrition and longevity studies became more sophisticated, experimental procedures also became more sophisticated. It has now been established that ies will compensate for nutrient density by altering overall consumption. One particularly rigorous study found that increasing nutrient density by vefold from a base diet less than doubled total food intake. Increasing nutrient density from ve- to tenfold above the base diet increased consumption only 33 % more, and increasing from 10 to 15-fold above the base diet did not alter food intake at all . To emphasize the diversity of y diets in use, the 15-fold higher density in this study is the standard diet in other studies. Now it is common for nutritional studies to include an array of food concentrations, both less than and more than, the standard diet for the lab. Fly research has shown most compellingly that macronutrient composition rather than calories alone has the most dramatic effect on longevity. The role of specic amino acids has not yet been completely claried, although as with laboratory rodents methionine appears to be a particularly important amino acid . Recently Piper formulated a chemi- cally dened diet for ies that should allow further renement of the relationship between nutrition and aging in this species . One particularly interesting discov- ery is that even the aroma of extra yeast is enough to shorten y lifespan . Nutritional research in ies has also illuminated a potentially serious confound in assessing genetic or even the pharmacological inuence on aging and longevity in studies that rely on ad lib feeding as virtually all do. The impact of a gene or a drug may be sensitive to dietary factors or may affect the amount of food eaten. Note, however, that the nutritional density of a normal diet varies dramatically among laboratories, such that what is considered a normal diet could affect whether the same mutation is a short-gevity or a longevity mutation and that at no food concen- tration is chico signicantly longer-lived than control ies on their optimal longevity diet (Redrawn from Clancy et al. As the food density of a normal diet in ies is completely arbitrary, the nding that this chico mutation extends life is a happenstance of a particular standard diet. Other labs would have observed the same mutation to be life-shortening under their standard condi- tions. As long as studies are performed over a broad range of food densities, this should not be a problem. However, genetic studies of longevity rarely examine a range of nutrient conditions. Worms can also be fed a chemically-dened, axenic diet , which avoids the problem of frank toxicity worms typically live much longer on an axenic versus an E. Surprisingly few worm studies use more than two feeding levels (control vs restricted) even though considerably more information can emerge from multiple feeding level studies . Several hundred worm genes signicantly extend life when wholly or partially inactivated. Given that the active forms of these genes were selected over millions of years of evolu- tion, this large number is surprising to say the least. It will be interesting if anything like this turns out to be true of other model organisms or whether this is a quirk of worm biology, perhaps due to the centrality of the dauer larval stage in its life his- tory. Still, some of the largest effects on worm longevity are still due to some of the earliest genes discovered to affect aging.
Xerosis can then be explained by cultural factures like frequent washing and use of aggressive soaps tadalis sx 20mg. This probably can be explained by the fact that the stratum corneum of black individuals is more compact and consists 20mg tadalis sx, though of same thickness tadalis sx 20 mg, of more layers  20 mg tadalis sx. Microscopic evaluation reveals that Black skin contains larger mast cell granules than Caucasian skin . It is tempting to speculate that this accounts for the observation that black patients report pruritus more frequently than other ethnic groups  . A pure physical property of the color of the black skin is that , especially in radiated heat (the sun) , it absorbs more heat than a lighter colored or white skin , resulting in more sweating in the dark-colored individual . Con- trary to what is often said, the density of eccrine sweat glands of black and white is the same. There may be some differences in the apocrine glands between the different ethnic groups: less dense in East Asians and more in Africans. In the cold, black skin radiates more heat, hence the tendency of black people to dress in warm clothes and to cover themselves at night. In particular, they cover their head, where the close-cropped hair allows the warmth to escape easily. Hair Hair differs in distribution, color and form among different ethnic groups [27 29]. The hair color of Blacks, Mongoloids, and Australoids is almost always black, while the color of Caucasian hair varies from deep black to blonde or reddish. The hair of Blacks is stiff and curly, that of Mongoloids is straight, while that of Caucasians is straight or wavy. The hairs leave the skin at an angle of 90 degrees in white individuals, but with a sharp corner in black individuals. Curly stiff hairs may cause problems, especially after shaving when the hairs curl inside the skin and cause inammation, as is seen in pseudofol- liculitis barbae and acne cheloidalis nuchae. The distribution of Black and Mongoloid hair often is less dense than that in Caucasians. There is some indication that the anchoring of Black hair is less strong, which may explain in part traction alopecia that is so often encountered in black patients. Many of these conditions can be linked to the racial or ethnical background of the indi- vidual, which is in part genetically related. Skin disorders peculiar to certain ethnic groups are nowadays designated as ethnic skin disorders. It is used for several reasons, including the fact that some groups of people do not t easily into a race. It is actually an imprecise concept, which implies shared origins, including cultural traditions that are maintained between generations, leading to a sense of identity in a group . Many ethnic skin disorders are diseases of pigmentation and discussed in Chap- ter 3. Nonpigmentary ethnic skin disorders are numerous, examples of which are lichen amyloidosis, common in Chinese people and keloid, seen especially in people from African descent. Most ethnic skin disorders are common in the countries of origin, so they are not specically related to migration. This chapter is about skin disorders that are induced by the change in environment. Both, skin diseases in immigrants from (sub)tropical countries to the temperate climatic zone as well as in tourists return- ing home from the (sub)tropics to the temperate climatic zone are dis- cussed. We have focused on disorders that are probably related to the new environment or to be more precise: to a lack of adaptation to the new environment. This is in fact a broad subject, with unfortunately a relative paucity of medical publications. In this chapter we have con- ned ourselves to a discussion of only a few disorders as an example of this topic. Inuence of the New Environment on the Skin 33 Other nonenvironmental factors determining the development of skin dis- eases are structure and function of the skin, immunological factors, and nally psychological factors, including behavior. Structure and function of the skin in people originating from tropical countries, are in some respects different from those of people from a tem- perate, less sunny climate . Molecular analysis has identied genetic dif- ferences between races and ethnic groups, probably related to differences in their environment. Most anthropologists believe that racial variation developed through natural selection processes: different biologic traits in the races developed because these traits facilitated adaptation to a partic- ular environment. Besides the difference in skin color, there are other anatomical differences in the skin between people from diverse regions of the earth. For example, dark-skinned people prob- ably have larger apocrine sweat glands and in greater numbers than white subjects. The stratum corneum of black people is more compact than that of white people, reecting a stronger intercellular cohesion, and this could be responsible for the fact that continuous scratching in black people often leads to lichenication. However, racial differences have been minimally investigated by objective methods and the data are often contradictory . The immune system, including the so-called skin immune system, plays a major role in defending the body against microbial intruders . In a new environment with microorganisms in the ecosystem that are immunolog- ically unknown to the traveler or immigrant, infectious diseases including skin infections can develop, which would not appear in the old environ- ment. According to the so-called hygiene theory, epidemiological and lab- oratory studies have implied that the environment during early childhood is important for the risk of developing atopic disorders. The prevalence of asthma, hay fever, and eczema among 1901 internationally adopted boys in Sweden was analyzed in relation to indicators of their early childhood environment. The adopted males who came to Sweden before 2 years of age suffered from asthma, hay fever, and eczema signicantly more often than those who came to Sweden between 2 and 6 years of age. This study demonstrates that environment during the rst years of life has a profound inuence on the risk of suffering from atopic disorders as young adults . Different social and cultural factors, both in immigrants moving from (sub)tropical to Western countries as well as in tourists traveling from Western countries to (sub)tropical regions can induce or contribute to var- ious (skin) diseases. Veiled women wearing covering clothes, often suffer from vitamin D deciency in Western countries. On the other hand, sun 34 Imported Skin Diseases bathing of tourists in (sub)tropical climates, could lead to massive sunburn and subsequent complications. In conclusion, from the aforementioned examples it should be clear that the interaction between factors present in a certain climatic zone on the one hand and biological traits and behavior of the individual on the other hand can induce new skin disorders in individuals coming from another climatic zone. Skin disorders in immigrants In this section we have described some examples of skin disorders in immi- grants from (sub)tropical countries to the temperate climatic zone, due to the change of environment. Skin diseases due to physical environmental factors Dry skin and dry eczema Dry skin or xerosis is one of the most common skin disorders in people from a warm humid tropical climate coming to a temperate climate. It is one of the skin disorders related to the humidity level in the new envi- ronment (Table 5. Dry skin and subsequently dry eczema can develop very soon after arrival, especially during wintertime. Furthermore, dry skin and dry eczema are more common in people taking frequent hot and long showers and using soap excessively. The natural oily coating on top of and within the horny layer of the epidermis, called natural skin emulsion is composed of an oily compo- nent and a watery component, produced by the skin itself. If this coating disappears, the skin loses water and may develop signs of the dry skin syn- drome. The accompanying symptoms are a dry feeling, itching (sometimes severe, even disturbing sleep), and sometimes pain. The disorder can be localized anywhere on the body, but most common are legs and arms, but also the face, especially the lips can be affected. It must however be differentiated from other types of eczema, for example, contact dermatitis and atopic dermatitis. An emollient or a urea-containing cream or ointment can be used as mainte- nance therapy. Finally, it is important to give the patient bathing and gen- eral advices: decrease the frequency and duration of showering; use warm, not hot water; do not use soap; dry the skin gently with a towel, patting is better than rubbing; use a hydrating ointment after drying the skin. Perniosis (chilblains) This is typically a disorder of wintertime, caused by an abnormal vascular reaction to cold in probably genetically predisposed persons. Immigrants from (sub)tropical countries, not using gloves and wearing inadequate footwear in the cold season are prone to perniosis. Psoriasis Lack of exposure to sunlight (visible and/or ultraviolet) in immigrants in Europe (or other temperate climate regions), coming from sunny (sub)tropical countries can induce or provoke diseases that would not have appeared if they had remained in their former sunny location. Examples (based on epidemiological studies and case reports) are seasonal mental depression , osteomalacia, and rickets . Based on experience in the Netherlands, we have the impression that psoriasis might be another example. Psoriasis is a common genetically determined chronic relapsing skin disorder, clinically characterized (in the white skin) by the presence of sharply delineated patches with erythema, thickening, and scaling. Its worldwide prevalence is approximately 1 3%, although it appears to be uncommon in certain populations, for example, South American Indians. It is suggested that it is less common in people from African descent than in Europeans. The typical localizations of lesions are the extensor sides of knees and elbows, the sacral region, and the scalp, but lesions can appear on virtually any part of the body. Lesions in dark-skinned people can sometimes cause difcul- ties in making the right diagnosis. A skin biopsy for histo- logical investigation can sometimes be helpful in making the right diagno- sis. People coming from (sub)tropical countries can have their rst episode of psoriasis after coming to Europe. Psychological stress related with the life in the new environment is another hypothetical explanation. Skin diseases related to biological and immunological factors Chickenpox (varicella) Chickenpox or varicella is a very contagious disease, caused by the varicella zoster virus. Chickenpox is common in certain immigrant groups coming from (sub)tropical countries to Europe or the United states. In a group of Tamil refugees to Denmark, 38% of the adults and 68% of the children developed chickenpox in the rst few months after arrival, due to lack of immunity . After a prodromal phase of 2 or 3 days with fever, malaise, and u-like symptoms, the skin eruption appears (Fig- ure 5. On a dark skin, the initial erythematous macules are obscure and after healing polka dot hyperpigmented scars can be present for many months and sometimes even years. These include secondary bacterial infection of the skin, otitis media, pneumoni- tis, and encephalitis. Typical prodromal symptoms and lesions on mucosal mem- branes can be helpful in making the right diagnosis. A denite diagnosis can be made by identifying the virus (or viral antigen) from a lesion or by antibody assessment. Chemical leukoderma Certain chemicals, particularly substituted phenols like p-tert- Butylphenol, are destructive to melanocytes and can so cause white patches in certain, possibly genetically predisposed persons . The diagnosis of industrial (chemical-induced) leukoderma should be suspected if a worker who potentially has been exposed to depigmenting chemicals develops white patches on the sites of exposure. It should be differentiated from other disorders with depigmentation, like idiopathic vitiligo and disorders with hypopigmentation, like postinammatory hypopigmentation. Anamnesis, including family history, inspection of the 40 Imported Skin Diseases whole body, and histology of a skin biopsy can be helpful in making the denite diagnosis. There is no specic treatment, but if there is a wish to treat, one can try treatment regimes that are advised for vitiligo. Skin disorders related to social and cultural factors Adverse reactions to skin bleaching Skin bleaching is a globally common but not very well-studied phe- nomenon among nonwhite persons, in particular women. They use various chemical skin-bleaching products to hopefully acquire a light skin. Clinical epidemiological reports show that skin bleaching is an imported phenomenon in European countries. There are indications that due to psychosocial pressure the bleaching practice is intensied in the new environment by some individuals in certain groups of immigrants: side effects of skin bleaching occur in immigrants in the Netherlands coming from Suriname, while it is unknown in this group in their country of origin . Use of skin bleaching products can lead to various adverse reactions, such as skin atrophy caused by corticosteroids and exogenous ochronosis caused by hydroquinone, the most widely used bleaching agent. It is a reticulated and ripple-like sooty pigmentation that must be differentiated from other types of hyperpigmentation like postinamma- tory hyperpigmentation and melasma. The histological picture is pathog- nomonic, with a dermal inltrate and yellow-brown banana shaped deposits in the H&E (hematoxylin and eosin) staining. Due to the hot and humid environment they can easily develop bacterial and fungal skin infections. In this section we have con- ned ourselves to discussion of miliaria and sunburn as common skin dis- orders in tourists after a holiday in the (sub)tropics, due to physical envi- ronmental inuences. Miliaria Miliaria or prickly heat is a disorder, commonly believed to be caused by blocking of the ducts of the eccrine sweat glands, probably by common skin bacteria like Staphylococcus epidermidis . However, according to Shuster, duct disruption, and not blockage is the immediate cause of the miliaria . Three types of miliaria are recognized, related to the level of the assumed obstruction: r Miliaria crystallina: In this case the obstruction is in the stratum corneum, causing tiny supercial blisters with clear uid that easily rupture. The lesions are localized espe- cially on the trunk, but can also be found on the head and neck region and the extremities. Complications are secondary bacterial infection, causing miliaria pustulosa or other types of pyoderma and disturbed heat regulation. It must be differentiated from fol- liculitis, which is characterized by follicular localized papules and pustules. No compelling reason to treat miliaria crystallina exists because this con- dition is asymptomatic and self-limited. The prevention and treat- ment of miliaria primarily consists of controlling heat and humidity so that sweating is not stimulated.
Surgical treatment tadalis sx 20mg, including nodovenous shunts and excision of redun- dant tissue can improve elephantiasis tadalis sx 20 mg. One of the most signicant advances in treatment has been the recog- nition that much of the progressive pathology is due to bacterial and fun- gal superinfection of tissues with impaired lymphatic function 20mg tadalis sx. Rigorous attention to hygiene of affected limbs and measures to improve lymphatic drainage reduce the frequency of larial fevers and even slowly improve lymphedema and elephantiasis 20 mg tadalis sx. Prevention Protection from mosquito bites through use of personal repellents , bed- nets , or insecticide-impregnated materials is prudent . Fifty-three endemic countries have started mass drug administration to interrupt transmission , representing the largest mass drug administra- tion program ever conceived . Single doses of the two drugs are given together at annual intervals and this needs to be repeated for at least 5 years . Loiasis Clinical picture Travelers to at-risk areas who stay for long periods of time are more likely to become infected than short-term travelers. Loiasis is often asymp- tomatic, though nonspecic symptoms of pruritus, pain or swelling of a limb, and urticaria can occur over several months as the fourth-stage lar- vae develop into adult worms. These are more common in expatriate Europeans and are thought to represent local hypersensitivity reactions to the subcutaneous passage of an adult worm. The adult worm can sometimes be seen temporarily as it passes across the eye underneath the conjunctiva causing irritation and unilateral palpebral edema, but eye-worm is more common in residents of endemic areas. Diagnostic procedures Parasitological methods Microlariae may be demonstrated in a Giemsa-stianed smear of daytime blood, with the sensitivity increased by passing the blood through a Milli- pore lter. Microlariae are not found in the blood before about 5 months after the onset of Calabar swellings and expatriates often have negative peripheral blood examination. The adult worm may be sur- gically extracted from the subcutaneous tissue or conjunctiva as a minor procedure. Immunological markers Infected travelers may have pronounced eosinophilia and high antilarilal antibodies but these are not specic tests. Histology A skin biopsy may sometimes reveal microlariae in dermal blood vessels. Long-term follow-up is necessary and retreatment should be considered if symptoms recur. Its use in immigrants from endemic areas may cause encephalopathy in patients with very high L. Mansonelliasis Clinical picture Mansonella infection can be asymptomatic or cause mild symptoms only. Laboratory-conrmed reports to the Health Protection Agency through national laboratory surveillance. Polderman & Lisette van Lieshout Leiden University Medical Center, Leiden, the Netherlands Key points r Skin Manifestations in Schistosomiasis: Each stage of infection may be accompanied by different skin manifestations: 1 Cercarial penetration may give rise to cercarial dermatitis. Common directly after exposure to cercariae of nonhuman schistosomes, in temperate zones. Themajor species involved are Schistosoma mansoni and Schistosoma japonicum,which inhabit the venules of the portal and mesenteric system, and Schistosoma haematobium that is found in the venous plexis of the urinogenital system. The characteristic feature of these helminths is that the adult worms are truly blood parasites but their offspring is excreted with stools or urine of the infected host. Only a part of the eggs produced manages to reach the intestinal lumen or the bladder cavity; many others do not successfully accomplish the migration from veins to intestines and bladder. They die en route and are the cause of subsequent pathology at the predilection sites or elsewhere. The adult worms are of a benign nature and do not normally cause any pathology . It involves a denitive and an intermediate host, two free-living stages, responsible for the infection of humans (cercariae) and snails (miracidia), and both a sexual and an asex- ual multiplication. The population biology is characterized by the facts that the free-living stages are extremely short-lived (less than 48 hours), the egg production is low (no more than approximately 300 eggs per gram feces per day in S. On average, worms are believed to live for 3 5 years but some sur- vive for 30 years or even longer. There are four different phases of the life cycle, and each causes a char- acteristic type of pathology and disease: 1 The penetration of cercariae through the intact human skin may result in so-called cercarial-dermatitis or swimmers itch. The onset of this phase may be as early as 2 weeks postexposure; it normally subsides by the time egg excretion starts, 7 10 weeks after the infection. The symptoms and signs of infection during that stage are caused by the immunopathological host reaction to schistosome eggs that get stuck in the tissues. Sometimes eggs get astray and get stuck in unusual sites: ectopic schistosomiasis may be the result. Transmission of schistosomiasis is restricted to the tropics and even there the distribution is highly focal. It is dependent on ecological conditions favorable or unfavorable for the survival and multiplication of the inter- mediate host snails. Clinical features The most prominent clinical features and the cause of signicant morbidity of schistosomiasis in endemic areas are the presence of (sometimes bloody) diarrhea, hepatomegaly, and splenomegaly in S. These manifesta- tions are largely associated with the intensity of present or past infection, that is, the worm load. First-line lab- oratory diagnosis is complicated by the fact that eggs are not excreted yet in the rst two phases of infection. During the phases of established and late chronic infection egg excretion may be very low and eggs are easily missed. Serology is useful in travelers normally living in nonendemic areas but of little help in endemic regions due to the long persistence of antibod- ies after clinically successful treatment. Skin manifestations Skin manifestations are not normally part of the clinical picture in estab- lished infections. Yet, they are occasionally seen in infections with each of the three species of human schistosomes. In the early phase of infection they are caused by cercarial penetration of the human skin, or by the aller- gic reaction as a component of the Katayama syndrome. Later they may be due to eggs in the genital system or to eggs that get astray, in situations referred to as cases of ectopic schistosomiasis. Cercarial dermatitis The duration of passage through the dermis is normally short. The cercariae lose their tail and the so-called schistosomulae rapidly pass the dermis to be transported to deeper layers. The clinical picture of cercarial dermatitis develops in a matter of minutes, and mostly within 1 hour Schistosomiasis 229 after penetration. In less than a day, the schistosomulae pass the skin and reach the lungs; the dermatitis vanishes and symptoms disappear within 2 3 days. In a highly endemic area in Congo, I used to be told by the local people that in particular sites exposure to the surface water was unhealthy because it caused itching. In those sites snail and cercarial concentrations were shown to be very high (personal observations). Mostly, however, this phase of infection with the human parasite remains unnoticed by the local population. The situation may be different when previously uninfected adults get exposed to (high densities of) cercariae. Intense itching shortly after swimming is commonly described by European or American visitors to endemic countries who are later shown to be infected . A history of cercarial dermatitis is reported in 10 36% of travelers later diagnosed with schistosomiasis . Cercarial dermatitis is much more intense when the cercariae belong to schistosome species unable to successfully develop in humans, such as those of Ornithobilharzia ocellata of birds. The schistosomulae of this and related species penetrate the human skin and migrate through the skin but fail to continue further development to adult worms. There is no specic means of diagnosis as antibodies have not been formed yet and eggs can of course not be found either. These brothers, developed an intensely itchy rash immediately after swimming at a beach near Boston. Itching occurred within minutes of leaving the water, blanching papules with central pustules developed several hours later, and small blisters appeared on day 3. Prostration, fever, profuse sweating, and eosinophilia are the accompanying signs of acute schistosome infection. Symptoms occur in approximately 50% of new infections and are seen 14 days to 3 months after exposure. Laboratory diagnosis depends on serology but may fail because serocon- version normally occurs 4 8 weeks after infection. Ectopic schistosomiasis The great majority of migrating schistosomules efciently reach their predilection sites in the urogenital system for S. Itisnot amazing that occasionally worms get astray during the process of migra- tion to their predilection sites and both adult worms and their eggs get stuck in aberrant sites. Young schistosomes require some time to rmly establish in their predilection site: S. In 1905, Symmers described a couple of copulating worms in the lung of an Egyptian person who died from the consequences of urinary schistosomiasis . In an extensive postmortem study in Egypt, schistosomal pulmonary emboli were demonstrated in one-third of all cadavers . Neuroschistosomiasis may be the result when granulomes develop around eggs in the central nervous system; skin manifestations arise from eggs deposited in the skin . Sometimes they are observed to slowly grow and to form warty or even cauliower projections . The skin lesions are most frequently found in the perigenital area of female patients. Anastomoses between the pelvic venous plexus and the subcutaneous plexus of the genitorectal area explain the relative frequency of skin lesions in that area. The occurrence of cutaneous lesions cannot be explained in one straight- forward way. The generally clustered nature of the papules suggests that adult egg-laying worms have been swept into abnormal foci. It has been stated that ectopic localizations of the lesions are a sign of a less sta- ble parasite host relationship. In a well- studied case of hyperpigmented lichenoid schistosome papules in the neck of a 12-year-old Nigerian boy, hematuria developed 3 weeks after presen- tation of the skin lesions . Feldmeier) schistosome infection may give rise to genital schistosomiasis as well. The presence of anastomoses between the plexus venosus uterovaginalis and the plexus venosus vesicalis explain the frequent occurrence of particularly S. Two different types of sandy patches are nowadays recog- nized: grainy sandy patches, linked to egg granulomas and yellow sandy patches, which may mimic a variety of sexually transmitted diseases. Epidemiological studies in sub-Saharan Africa indicate that between 33% and 75% of S. Diagnosis is based on recognition of the sandy patches in colposcopy, and/or the demonstration of S. The cure rate of a standard dose of praziquantel (once 40 mg/kg) depends on the worm load but is denitely less than 100%. Apart from praziquantel to kill the egg producing adult worms, additional treatment to cope with Schistosomiasis 233 abscess-forming inammation may be needed. In patients with a pro- nounced swimmers itch, an oral antihistamine and topical steroids might be indicated. In patients with Katayama syndrome, treatment is generally postponed until egg production starts, since praziquantel is inefcient in infections with immature stages of the parasite. Recent studies suggest arthemeter might be effective in very recent infections . In patients with skin or genital lesions caused by schistosome eggs trapped in the tis- sues, praziquantel is the drug of choice. Lesions, however, do not resolve quickly after successfully removing the adult egg-laying schistosomes. Introduction Tungiasis is a parasitic skin disease due to the penetration of the female sand ea Tunga penetrans into the epidermis of its host and its subsequent development. Once embedded in the stratum corneum, the ea undergoes a peculiar hypertrophy, during which the abdominal segments enlarge to the size of a pea. Through a tiny opening in the skin hundreds of eggs are expelled for a period of about 3 weeks . Three to four weeks after penetration, the parasite dies in situ and eventually is sloughed from the epidermis by tissue repair mechanisms. However, in individuals, living in an endemic area, rein- festation is the rule and sequels are common. Repeated infestation leads to a chronic inammation of the foot with persistent pain and difculty of walking . The rst description of the disease was provided by Hans Staden von Homberg zu Hessen, a Imported Skin Diseases, Second Edition. Being comparatively rare in travelers, the ectoparasitosis is frequently misdiagnosed and patients are subjected to inappropriate diagnostic and therapeutic procedures. There is anecdotal evidence that the ea was introduced to Angola with ballast sand of a sailing ship that left Brazil in 1872. At the end of the nineteenth century the parasite had reached East Africa and Madagascar. Today, tungiasis is found on the American continent from Mexico to northern Argentina, on several Caribbean islands, as well as in almost every country of sub-Saharan Africa . In endemic countries, the distribution of tungiasis is uneven and most cases occur in circumscribed foci. In resource-poor communities, prevalence may be up to 50% in the general population . Prevalence and parasite burden are related, and in typical foci, individuals may harbor between a few and more than 100 sand eas . There is a clear seasonality in incidence with only few cases occurring during the rainy season and a high attack rate during the dry season .
On the other hand there is a pressing duty to inform known individuals of a serious avoidable health risk 20 mg tadalis sx, and prevent further transmission tadalis sx 20 mg. It is good practice to discuss difficult choices with colleagues 20mg tadalis sx, and document the reasons for the decisions made tadalis sx 20mg. An evaluation of costs and outcomes for provider referral for Clamydia trachomatis . The best use can be made of existing resources by prioritising the most effective activities . The need for additional resources Audit findings can provide the evidence base for a case of need . The need for better liaison Audit may draw attention to difficulties within the multidisciplinary team , or between clinics . Achievement The feedback provided by an outcome audit may increase motivation , morale and job satisfaction. Support and guidance may be available from the local audit department, or medical colleagues. Difficulties may be minimised if health advisers are directly involved in all stages of partner notification audit. Design Beginning with clear, precise questions will help to identify the types of data needed. The methodology selected would be able to produce reliable and valid information: retrospective case- note review is only appropriate if all required information is likely to have been documented in all cases; prospective studies, on the other hand, may mislead because staff behaviour can be influenced by the monitoring process. Data collection Piloting the audit tool will check that there is a place to record all findings. There may be a risk of bias if the recorder has a vested interest in a particular outcome. Data analysis The process and outcome standards recommended below are measured using simple mathematics, and are manageable by health advisers. The local audit department or medical colleagues may be able to help if more complex analysis is required for locally designed audits. Data interpretation To avoid the risk of bias and/or subsequent conflict, a representative of all affected staff groups would be involved in discussion. Recommendations These would reinforce practices that are working well and identify areas where change may bring improvements. Action Findings would be fed back to all concerned and recommendations acted upon. Re-audit Further audit would be required to assess whether the implemented changes have been effective. Staff support Access to regular management and clinical supervision is recommended. Opportunities to discuss difficult aspects of their work with other health advisers and a consultant physician may also be beneficial. Office accommodation At least one designated health adviser office is required for administration and storage. A cordless phone is useful to permit movement between quiet areas for sensitive discussion and a computer terminal for booking appointments. Answer machine An answer machine on the ex-directory health adviser line will reduce the number of missed calls from patients, contacts or other clinics. Desk spaces To ensure adequate record keeping and organisation, each health adviser needs their own desk space. Internet and email facilities An internet facility provides access to relevant data; email assists communication with colleagues, patients and contacts. It is essential to be sure that the best use is made of resources, that the methods used are locally effective and that time is not being wasted on unproductive activities. The following standards for good practice offer suitable criteria for auditing the partner notification process: Table 6. However, outcomes can not be taken as a proxy measure of health adviser performance: 58 variable local factors, including population demographics and mobility, sexual mixing patterns and local service provision all influence the success of partner notification. Positive results at test of cure are counted as additional cases unless treatment failure is suspected. Clinics serving stable populations might expect to exceed this target by at least 50% Time span The time span of 90 days is deliberately generous to allow all successes to be counted. In practice there will be an emphasis on securing contact attendance as soon as possible. Verification Attempts to verify attendance are recommended because patient reports may be unreliable. A separate record of the additional number of contacts whose attendance was reported but not verified might be useful, although these would not be counted in the above total. This will increase the knowledge base to strengthen and guide professional activity. Many endeavoured to establish rigorous methods that respected the rights of patients and contacts to a sensitive and confidential service. There is however a genuine desire within health advising to critically examine practice in order to refine policies and procedures. In the realm of patient care, it is implicit in evidence-based medicine that two basic principles are respected: Evidence alone is insufficient in itself to make clinical decisions 3 A hierarchy of evidence sets out to guide decision-making Not all health adviser work will easily fall under the spotlight of the research scientist and indeed in some areas this would be wholly inappropriate. It is also acknowledged that methodological pitfalls abound when undertaking research into the sensitive and largely 4 private arena of sexual activity. Dutch and British studies identify factors that hinder partner 8 9 10 11 12 13 notification. Large-scale randomised controlled trials in measuring the 14 effectiveness of alternative partner notification strategies are therefore needed Casual or one-night-stand partners, gay men, commercial sex worker clients, teenagers and ethnic minorities are variously cited as difficult to reach with traditional contact tracing methods. Traditional health promotion strategies with gay and bisexual men are held to have had limited impact on infection transmission. Partner notification takes on a greater significance in the light of such evidence. More studies looking at basic gender 16 issues in partner notification are needed There is scope for triangulated methods to be employed in this area. This term is used in a research context to describe the use of a variety of data sources or methods to examine a specific phenomenon either simultaneously or sequentially in order to produce a more accurate account of the phenomenon under investigation. It would be interesting to explore variables such as gender, sexual orientation, diagnosis, relationship status and age on partner notification outcomes. Qualitative studies can bring a richness and depth to data collected through quantitative designs. Major limitations exist in the recruitment and retention of subjects for cohort studies. They hold potential nevertheless to capture outcomes other than attendance rates and diagnosis. What other measures do health advisers adopt to follow up patients that may only attend once? It is not known Studies of partner notification for gonorrhoea have associated health adviser resources with outcomes. Clinics with poorer partner notification outcomes may be as a result of greater workloads, fewer interview rooms or desk spaces, and less health adviser 21 experience. Do health advisers have good access to the Internet and email and harness their potential for tracing partners? No study could be found that measured the ethical consequences of alternative partner notification strategies. A longitudinal survey study to examine the impact of coming into a contact tracing programme could reveal fascinating insights as yet unrecorded by researchers Practitioner research in this area is to be encouraged due to their insider position of easier access to patients. The use of videos, 27 leaflets, nurse counsellors and lay counsellors require further investigation. The use of community pharmacies and other innovative methods of ensuring partners receive empirical 30 treatment could be looked at Training of personnel in more effective interviewing skills is encouraged (Grade 31 32 33 C). Health advisers are key stakeholders in the process of improving standards through the application of evidence-based research. More attention paid within the profession to facilitate research projects will prove to be invaluable. This fact ought to be addressed and resources made available to reverse this trend. As time progresses and opportunities are taken to conduct more research, sexual health advisers will have greater confidence that their work is influenced by the firmer foundation of research findings than custom and practice. Partner notification for sexually transmitted diseases: an overview of the evidence. Sex difference in partner notification: results from three population based surveys in France. Sex Transm Dis 1997; 24: 511-18 24 Ramstedt K, Halligen B, Britt-Inger L, Hakansson C. Evaluation of a video based health education strategy to improve sexually transmitted disease partner notification in South Africa. Over-the-counter advice for genital problems: the role of the community pharmacist. Roles for pharmacists in the prevention and control of sexually transmitted diseases. Sex Transm Dis 1999 Apr;26(4 Suppl):S44-7; discussion S48 31 Department of Health. With this they help people make informed choices for themselves and their sexual partners. Detailed information can be found in the medical literature and it is vital that health advisers keep up to date with current research findings published in professional journals. The recommendations for partner notification (Grade C) in each condition are outlined and summarised in table 8. In general it should be noted that: Some conditions merit the offer of a provider referral (for definition see Ch. Sexually transmissible - Describes infections and conditions that could be passed on through intimate sexual contact but can also be present independent of sexual activity such as candida, scabies, molluscum contagiosum. It emphasises the part played by sex in the spread of diseases that would not otherwise be considered as a single group. These two infections along with 2 chancroid constitute the legally defined venereal diseases in British law. Mycoplasmas These are bacteria but they do not have rigid cell walls - mycoplasmas and chlamydiae can be responsible for non-gonococcal urethritis (including chlamydial) and cervicitis. Protozoa Single-celled microscopic forms of animal life - responsible for trichomoniasis. Metazoan All other parasitic animal life forms - causing scabies and pediculosis pubis (pubic lice or crabs ). In women, highest rates of gonorrhoea are in those aged 16 to 19 years and, in 2000, 41% of females with gonorrhoea were aged under 20. Gram-negative diplococcus Infection sites Primary- Mucous membranes of the urethra, endocervix, rectum, pharynx. There is no evidence to show that it can be passed on from toilet seats or sharing towels and cups. It can be spread to the eyes from the genitals via the fingers Infection to detection period Symptoms of infection may show up at anytime between 1 and 14 days Table 8. Rectal infection in homosexual Urethral infection may cause dysuria (12%) men may cause anal discharge but not frequency. Pharyngeal infection is usually Pharyngeal infection is usually asymptomatic asymptomatic (>90%). Complications Spread from the urethra or endocervix to involve the epididymis and prostate in men (1% or less) and the endometrium and pelvic organs in women (probably <10%). Dissemination may also occur from infected mucous membranes, resulting in skin lesions, arthralgia, arthritis and tenosynovitis. Offer provider referral 69 Sexual contacts are to be screened and treated for gonorrhoea and chlamydia infections using the following criteria applying to the index case; a. Highest rates of diagnosis are seen in young people, particularly women in the 8 16 to 19 and 20 to 24 year age groups. Vertical transmission to baby during delivery Infection to detection period 1 to 3 weeks after exposure Table 8. Offer provider referral Sexual contacts are to be screened and treated for chlamydia infections using the following criteria: o 4 weeks prior to the onset of symptoms in men o 6 months, or until the last previous sexual partner (whichever is the longer time period) for all women and asymptomatic men o A policy of current partner and previous one (1 + 1) can be applied to chlamydia infections 9 10 11 Syphilis Following nearly two decades of consistent decline in England, numbers and 12 rates of infectious syphilis have been steadily increasing since 1997. Rates have increased 13 sharply in males aged 20 to 44 years old and in females aged 16 to 34 years old. A systemic disease Classification Syphilis is classified as acquired or congenital Acquired syphilis is divided into: Early (primary, secondary and early latent. Greater than 2 years) Tertiary including gummatous, cardiovascular and neurological involvement The latter two are also sometimes classified as quaternary syphilis Congenital syphilis is divided into: Early (first 2 years) Late (including stigmata of congenital syphilis) Transmission Sexual transmission occurs only when mucocutaneous syphilitic lesions are present. However 46-60 % of contactable sexual partners of patients and pregnant women with early syphilis also have the infection Incubation period Up to 90 days 71 Table 8. Classically single, painless and indurated with a clean base discharging clear serum in the anogenital region. However they may be atypical and present as multiple, painful, purulent, destructive and extragenital. Secondary Syphilis Multisystemic involvement within the first two years of infection. It is classically non-itchy but may be itchy, particularly in dark-skinned patients. Offer provider referral Transmission is uncommon after the first year of infection. The causes Chlamydia (30-50% of cases) Ureaplasma urealyticum (ureaplasmas) and Mycoplasma genitalium (10-20% of cases respectively) Trichomonas vaginalis has been reported in 1-17% cases N.
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